RQT complex:K63polyUb-80S ribosome dissociates yielding K63polyUb-40S subunit and 60S subunit:peptidyl-tRNA with nascent peptide

Stable Identifier
R-HSA-9948300
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
RQT complex:K63polyUb-80S ribosome dissociates yielding K63polyUb-40S subunit and 60S subunit:peptidyl-tRNA with nascent peptide
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
The ribosome quality control trigger (RQT) complex (ASCC2:TRIP4:ASCC3, homologous to the CUE3:RAT4:SLH1 complex from yeast, Sitron et al. 2017, Matsuo et al. 2017), splits stalled 80S K63-polyubiquitinated ribosomes into 60S subunits and K63-polyubiquitinated 40S subunits (Hashimoto et al. 2020, Juszkiewicz et al. 2020, Narita et al. 2022, Miścicka et al. 2024). The cryo-EM structure of the CUE3:RAT4:SLH1 complex in yeast indicates that the SLH1 subunit (homologus to ASCC3) may apply an ATP-powered pulling force on the mRNA to dissociate the 80S ribosome into 40S and 60S subunits (inferred from yeast homologs in Best et al. 2023). The peptidyl-tRNA containing the nascent peptide remains at the P site of the 60S subunit. The mRNA dissociates from the ribosomal subunits and is thought to be degraded at this time. In the case of collided yeast ribosomes, the mRNA is first endonucleolytically cleaved by Cue2 (mammalian homolog N4BP2) and the cleavage products are exonucleolytically degraded by XRN1 and the exosome (Ikeuchi et al. 2019).
Literature References
PubMed ID Title Journal Year
32099016 Identification of a novel trigger complex that facilitates ribosome-associated quality control in mammalian cells

Hashimoto, S, Sugiyama, T, Yamazaki, R, Nobuta, R, Inada, T

Sci Rep 2020
36302773 A distinct mammalian disome collision interface harbors K63-linked polyubiquitination of uS10 to trigger hRQT-mediated subunit dissociation

Narita, M, Denk, T, Matsuo, Y, Sugiyama, T, Kikuguchi, C, Ito, S, Sato, N, Suzuki, T, Hashimoto, S, Machová, I, Tesina, P, Beckmann, R, Inada, T

Nat Commun 2022
32579943 The ASC-1 Complex Disassembles Collided Ribosomes

Juszkiewicz, S, Speldewinde, SH, Wan, L, Svejstrup, JQ, Hegde, RS

Mol Cell 2020
38366554 Ribosomal collision is not a prerequisite for ZNF598-mediated ribosome ubiquitination and disassembly of ribosomal complexes by ASCC

Miścicka, A, Bulakhov, AG, Kuroha, K, Zinoviev, A, Hellen, CUT, Pestova, TV

Nucleic Acids Res 2024
Participants
Input
Output
Participates
as an event of
Catalyst Activity

ATP hydrolysis activity of RQT complex:K63polyUb-80S Ribosome:no-go mRNA:peptidyl tRNA with nascent peptide [cytosol]

Physical Entity
RQT complex:K63polyUb-80S Ribosome:no-go mRNA:peptidyl tRNA with nascent peptide [cytosol] (Homo sapiens)
Activity
ATP hydrolysis activity (GO:0016887)
Authored
May, B  (2025-05-19)
Reviewed
Bennett, EJ  (2025-08-09)
Ford, PW  (2025-08-09)
Jafarnejad, SM  (2025-11-07)
McGirr, T  (2025-11-07)
Created
May, B  (2025-05-19)
Cite Us!